Monoclonal antibodies (mAbs) have been successfully employed to target a wide range of therapeutic areas over the last two decades (Walsh G., Nature biotechnology 2014; 32:992-1000; Lawrence S. Nature biotechnology 2007; 25:380-2). Protein aggregation remains a major concern in the production of monoclonal antibodies and other therapeutic proteins. Due to potential impact on potency and immunogenicity, it is important to understand the aggregation mechanism so that appropriate control strategies can be implemented to assure product quality.
Mapping the dimerization interface in mAb molecules remain challenging, due to the complexity and heterogeneity of mAb dimers. Although hydrogen-deuterium exchange mass spectrometry (HDX MS) has been successful in studying protein-protein interactions, little success has been achieved in revealing the mAb dimerization interface, presumably due to the method limitations in detecting protein side-chain interactions.
Thus, it is an object of the invention to provide systems and methods for mapping heterogeneous dimerization interfaces of proteins.
It is another object of the invention to provide protein drug products with reduced levels of dimerization.
It is still another object of the invention to provide methods of producing protein drug products having reduced dimerization.